Can Hepatitis A Vaccine Cause Injury & Death?
The Institute of Medicine (IOM) has acknowledged that there is individual susceptibility to vaccine reactions for genetic, biological and environmental reasons, but that vaccine providers cannot accurately predict prior to a vaccine’s administration who will suffer complications, injury or death from vaccination.1 However, a person who has previously had a serious reaction to a vaccination or is acutely or chronically ill should become informed about all potential risks associated with vaccination and discuss any concerns with a trusted health care professional before receiving a hepatitis A vaccine or any other vaccine.
According to the CDC, possible side effects from the hepatitis A vaccine include: 2
- Redness or pain at the injection site
- Persistent severe shoulder pain
- Allergic reaction
VAQTA: Adverse events reported to have occurred during pre-licensing clinical trials of Merck’s VAQTA hepatitis A vaccine included: injection site warmth, bruising, pain, redness, and swelling; headache; fever; bronchial constriction; asthma; wheezing; swelling/edema; generalized redness; rash; eye irritation; itching; dermatitis; irritability; diaper dermatitis; upper respiratory infection; diarrhea; teething; rhinorrhea; vomiting; constipation; otitis media; insomnia; nasopharyngitis; rhinitis; viral infection; croup; Streptococcal pharyngitis; laryngotracheobronchitis; viral exanthema; viral gastroenteritis; roseola; anorexia; febrile seizure; dehydration; cellulitis and insomnia.3
Serious complications reported by Merck in the VAQTA product insert during vaccine post-marketing surveillance have included: Diarrhea/gastroenteritis; thrombocytopenia; Guillain-Barre Syndrome; encephalitis and cerebellar ataxia. 4
In all of Merck’s pre-licensing clinical safety trials involving children under the age of 2, VAQTA vaccine was administered either alone, or in combination with additional vaccines. No pre-clinical safety studies were ever completed to compare the health outcomes of VAQTA against a true placebo or even against another previously licensed vaccine. In one study, vaccine recipients received either VAQTA vaccine alone or else VAQTA vaccine in combination with Merck’s ProQuad (Measles-Mumps-Rubella-Varicella) vaccine, a vaccine found to be associated with an increased risk of febrile seizures,5 6 along with Wyeth’s Prevnar vaccine, for the first dose of the vaccine. For the second dose of the vaccine, pre-licensure clinical trials compared the safety of VAQTA vaccine against the safety of VAQTA vaccine administered in combination with Merck’s highly reactive ProQuad vaccine. An additional clinical safety trial compared health outcomes of children who received either VAQTA alone or else VAQTA in combination with Merck’s Haemophilus B Conjugate Vaccine, PedvaxHIB or both PedvaxHIB and GlaxoSmithKline’s Infanrix, a diphtheria, tetanus and acellular pertussis vaccine. Health outcomes of clinical trial vaccine recipients were monitored for only 2 weeks. 7
In pre-licensing clinical trials involving children between the ages of 2 and 18 years of age, clinical trial participants received either VAQTA or a dose of amorphous aluminum hydroxyphosphate sulfate, an aluminum adjuvant linked to adverse events and associated with autoimmune/autoinflammatory conditions.8 In this particular clinical trial, the second dose of the aluminum adjuvant was not administered to the control group because “code for the trial was broken.” 9 As with pre-licensing clinical trials involving children under the age of 2 years of age, the health outcomes of the clinical trial participants were limited to 14 days. 10
Only 240 healthy adults ages 19 and older were studied in the initial VAQTA vaccine pre-licensing clinical trials and participants received either VAQTA alone, or VAQTA in combination with the Typhoid Vi polysaccharide vaccine and the yellow fever vaccine. Four additional clinical trials involving 1,645 healthy adults compared VAQTA against differing amounts of viral antigens of hepatitis A and/or aluminum, VAQTA when administered alone or in combination with hepatitis A immune globulin, three different lots of VAQTA vaccine, and VAQTA against differing amounts of the hepatitis A viral antigens. Again, the evaluation of health outcomes of the pre-licensing clinical trial participants were limited to 14 days.11
HAVRIX: Adverse events reported to have occurred during pre-licensing clinical trials of GlaxoSmithKline (GSK) HAVRIX hepatitis A vaccine included: injection site warmth, bruising, pain, redness, induration, and swelling; headache; fever; anorexia; nausea; fatigue; malaise; vertigo; photophobia; lymphadenopathy; dysgeusia; hypertonia; rash; urticaria; pruritus; abdominal pain; diarrhea; vomiting; insomnia; muscle and joint pain; pharyngitis; upper respiratory infections; seizure; bronchial hyper-reactivity and respiratory distress.12
Serious complications reported by GlaxoSmithKline (GSK) in the HAVRIX product insert during vaccine post-marketing surveillance have included: rhinitis; vasculitis; hepatitis; jaundice; anaphylaxis and anaphylactoid reactions; serum sickness-like syndrome; thrombocytopenia; shortness of breath; dizziness; vasculitis; shortness of breath; multiple sclerosis; Guillain-Barre Syndrome; musculoskeletal stiffness; injection site reaction; local swelling; paresthesia; encephalopathy, syncope, myelitis, neuropathy, angioedema, erythema multiforme, hyperhidrosis, chills, influenza-like symptoms and congenital anomaly.13
The HAVRIX vaccine package insert reports that clinical trials involving the vaccine have occurred in over 37,000 individuals, however, GSK provides very limited information on these trials in their vaccine product insert. The only study detailed as part of its package insert, HAVRIX Study 231, involved 1,241 healthy children between the ages of 11 and 25 months.14 Safety studies in this clinical trial compared the health outcomes of individuals receiving HAVRIX alone, HAVRIX in combination with Merck’s MMR vaccine and Merck’s varicella vaccine, or MMR and Varicella vaccine followed by a dose of HAVRIX vaccine 42 days later. Solicited adverse events such as fever, irritability, drowsiness, loss of appetite, redness, pain, and swelling were recorded by parents on diary cards for 3 days following vaccination and submitted to clinical trial monitors. Information on unsolicited adverse events occurring between Day 4 and Day 31 post vaccination were collected from the parents of trial participants and a telephone follow up occurred 6 months later. While the vaccine product insert provides limited information on health outcomes of the 1,241 trial participants, further data on this particular study was released in February of 2013 as part of GSK’s “commitment to further clinical transparency through public disclosure of GSK Clinical Study Reports (CSRs) on the GSK Clinical Study Register.”15
According to the clinical trial documents of HAVRIX Study 231 released by GSK in 2013, over 62 percent of trial participants receiving HAVRIX alone, nearly 58 percent of trial participants receiving HAVRIX in combination with MMR and varicella vaccine, and over 66 percent of participants receiving MMR and varicella vaccine followed by HAVRIX at Day 42, experienced an adverse reaction in the first 30 days following vaccination.16 Of the 1,241 children who participated in this clinical trial, 51, or 4 percent, experienced a serious adverse event following vaccination, with half of those serious reactions occurring in children who received HAVRIX in combination with the MMR and varicella vaccine.17 In the United States, the hepatitis A vaccine is routinely administered with the MMR, varicella, and pneumococcal vaccines, in accordance to the CDC’s recommended vaccine schedule.18
Details on the serious adverse events that occurred during HAVRIX Study 231 remain unknown, as the information was redacted by GSK prior to release. The document, however, reports that one serious adverse reaction, a diagnosis of autism following vaccination with HAVRIX in combination with the MMR and varicella vaccine, “was considered by the investigator to have a possible causal relationship to vaccination.” 19
The HAVRIX Study 231 document released by GSK also noted that a diagnosis of or suspected immunodeficient condition such as HIV or a newly diagnosed neurologic disorder, in addition to other possible medical events that occurred during the clinical trial, would result in the removal of the individual’s results from the study’s final outcome.20 1,474 children were initially enrolled in the study, however, final data includes the outcomes of only 1,241 children. In the Study 231 document, GSK states that four children who suffered adverse events were removed from the study and that seven others were eliminated for “other reasons”, with further details redacted by GSK.21
TWINRIX: Adverse events reported to have occurred during pre-licensing clinical trials of GlaxoSmithKline (GSK)’s TWINRIX hepatitis A/ hepatitis B vaccine included: injection site redness, pain, induration, and swelling; headache; fatigue; nausea; diarrhea; vomiting; upper respiratory infections; insomnia; anorexia; dizziness; migraine; paresthesia; somnolence; syncope; vertigo; muscle and joint pain; back pain; constipation; weakness; agitation; irritability, abdominal pain; influenza-like illness; erythema; petechiae; rash; sweating; urticaria; lymphadenopathy; dysgeusia; hypertonia; tingling; migraine; flushing; photophobia and hypotension.22
Serious complications reported by GSK in the TWINRIX product insert during vaccine post-marketing surveillance have included: meningitis, herpes zoster; allergic reaction, anaphylactoid reaction, anaphylaxis, serum sickness–like syndrome days to weeks after vaccination (including arthralgia/arthritis; fever; urticaria; erythema multiforme; ecchymoses; and erythema nodosum) thrombocytopenia; thrombocytopenic purpura; Bell's palsy; convulsions; encephalitis; encephalopathy; Guillain-Barré Syndrome; myelitis; multiple sclerosis; neuritis; neuropathy; optic neuritis; paralysis; paresis; transverse myelitis; hepatitis; jaundice; shortness of breath; bronchospasm, including asthma-like symptoms; conjunctivitis; visual disturbances; earache; tinnitus; palpitations; tachycardia; vasculitis; dyspepsia; arthritis; alopecia; eczema; erythema multiforme; erythema nodosum; hyperhidrosis; lichen planus and muscular weakness.23
Pre-licensure clinical trials of TWINRIX, a bivalent vaccine combining HAVRIX (inactivated Hepatitis A vaccine) and ENGERIX-B (recombinant Hepatitis B vaccine), were limited to approximately 2,500 trial participants. In the United States, TWINRIX was studied for use in only 773 healthy adults between the ages of 18 and 70. In this U.S. pre-clinical vaccine trial, study participants received either TWINRIX, a dose of HAVRIX (hepatitis A vaccine), a dose ENGERIX-B (Hepatitis B vaccine), or a dose of both HAVRIX and ENGERIX-B. Adverse events such as fever, irritability, and drowsiness, loss of appetite, redness, pain, and swelling were actively solicited by clinical trial monitors for only 3 days following vaccination. Data on unsolicited adverse reactions were collected between Day 4 and Day 31 following vaccine administration. GSK reports that the data collected from U.S. clinical trials were comparable to those reported from other clinical trials, however, this data has not been published. Adverse events reported during the pre-licensure clinical trials included injection site redness, swelling, and induration, agitation, insomnia, abdominal pain, vomiting, anorexia, respiratory tract infections, vertigo, dizziness, migraine, rash, weakness, and more.24
In the comprehensive report evaluating scientific evidence, Adverse Effects of Vaccines: Evidence and Causality25, published in 2012 by the Institute of Medicine (IOM), eight reported vaccine adverse events following the hepatitis A vaccine were evaluated by a physician committee26. These adverse events included acute disseminated encephalomyelitis, transverse myelitis, multiple sclerosis, Guillain Barre Syndrome, chronic inflammatory disseminated polyneuropathy, Bell’s palsy, anaphylaxis, and autoimmune hepatitis.
Of the eight vaccine-related adverse events evaluated, the IOM committee concluded that there was inadequate evidence to support or reject a causal relationship between the hepatitis A vaccine and all eight vaccine related adverse events, because of the complete absence of methodologically sound published studies required to make a determination.27
A 2011 published study linked hepatitis A vaccination to Henoch-Schönlein purpura, a disorder that causes bleeding and swelling of the small blood vessels.28 In 2012, an epidemiological study examining the risk of immune thrombocytopenic purpura (ITP), a blood disorder causing unusually low levels of platelets in the body, following vaccination found a significantly higher number of reported cases in individuals between the ages of 7 and 17 following vaccination with the hepatitis A vaccine. The study authors recommended further research on this association, however, no additional studies have been published.29
Acute disseminated encephalomyelitis (ADEM) combined with acute motor axonal neuropathy following the hepatitis A vaccine and an infection with Campylobacter jejuni, a bacteria commonly associated with food poisoning, was documented in a 1999 published case study.30 In 2009, doctors from Singapore submitted a case report of retrobulbar optic neuritis in an HIV positive man following vaccination with the hepatitis A vaccine.31
Using the MedAlerts search engine, as of as of March 31, 2020, there have been more than 43,130 reports of hepatitis A vaccine reactions, with over 25 percent (10,916) of reaction occuring in children under 3 years of age. Reports made to the federal Vaccine Adverse Events Reporting System (VAERS) note hospitalizations, injuries and deaths following hepatitis A vaccinations, including 152 related deaths, 3,393 hospitalizations, and 904 related disabilities. However, the numbers of vaccine-related injuries and deaths reported to VAERS may not reflect the true number of serious health problems that occur after hepatitis A vaccination.
Even though the National Childhood Vaccine Injury Act of 1986 legally required pediatricians and other vaccine providers to report serious health problems following vaccination to federal health agencies (VAERS), many doctors and other medical workers giving vaccines to children and adults fail to report vaccine-related health problem to VAERS. There is evidence that only between one and 10 percent of serious health problems that occur after use of prescription drugs or vaccines in the U.S. are ever reported to federal health officials, who are responsible for regulating the safety of drugs and vaccines and issue national vaccine policy recommendations.32 ,33 ,34 ,35 36
On December 1, 2004, hepatitis A vaccine was added to the National Vaccine Injury Compensation Program's (VICP) Vaccine Injury Table, as published in the Federal Register. As of May 1, 2020, there had been 155 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following hepatitis A vaccination, including 7 deaths and 148 serious injuries. Of that number, the U.S. Court of Claims administering the VICP has compensated 76 children and adults, who have filed for hepatitis A vaccine injury.37
IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.
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1 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality. Evaluating Biological Mechanisms of Adverse Events (p. 57-102), Increased Susceptibility (p. 82). Washington, DC: The National Academies Press 2012.
2 CDC Hepatitis A VIS July 20, 2016
3 FDA VAQTA Product Insert Dec. 20, 2018
5 MacDonald SE, Dover DC, Simmonds KA, et al. Risk of febrile seizures after first dose of measles–mumps–rubella–varicella vaccine: a population-based cohort study. CMAJ. 2014 Aug 5; 186(11): 824–829.
6 Ma SJ, Xiong YQ, Jiang LN et al. Risk of febrile seizure after measles-mumps-rubella-varicella vaccine: A systematic review and meta-analysis. Vaccine. 2015 Jul 17;33(31):3636-49
7 FDA VAQTA Product Insert Dec. 20, 2018
8 Mold M, Shardlow E, Exley C Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations Sci Rep. 2016; 6: 31578.
9 FDA VAQTA Product Insert Dec. 20, 2018
12 FDA HAVRIX Product Insert Dec. 19, 2018
15GlaxoSmithKline Clinical Study Report for Study 208109/231 (HAV-231). Feb. 10, 2011
16 GlaxoSmithKline Clinical Study Report for Study 208109/231 (HAV-231). Feb. 10, 2011. Page 10.
17 GlaxoSmithKline Clinical Study Report for Study 208109/231 (HAV-231). Feb. 10, 2011. Page 11
18 CDC 2019 Recommended Vaccinations for Infants and Children (birth though 6 years) Parent-Friendly Format Feb. 5, 2019
19 GlaxoSmithKline Clinical Study Report for Study 208109/231 (HAV-231). Feb. 10, 2011. Page 11
20 GlaxoSmithKline Clinical Study Report for Study 208109/231 (HAV-231). Feb. 10, 2011. Page 44
21 GlaxoSmithKline Clinical Study Report for Study 208109/231 (HAV-231). Feb. 10, 2011. Page 71
22 FDA Twinrix Product Insert Dec. 18, 2018
25 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality. (Evaluating Biological Mechanisms for Adverse Events: Increased Susceptibility). Washington, DC: The National Academies Press. 2012
26 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality. (Evaluating Biological Mechanisms for Adverse Events: Increased Susceptibility). Washington, DC: The National Academies Press. 2012. Chapter 7: Hepatitis A.
28 Jariwala S, Vernon N, Shliozberg J. Henoch-Schönlein purpura after hepatitis A vaccination. Ann Allergy Asthma Immunol. 2011 Aug;107(2):180-1.
29 O'Leary ST, Glanz JM, McClure DL et al, The risk of immune thrombocytopenic purpura after vaccination in children and adolescents. Pediatrics. 2012 Feb;129(2):248-55
30 Huber S, Kappos L, Fuhr P, et al. Combined acute disseminated encephalomyelitis and acute motor axonal neuropathy after vaccination for hepatitis A and infection with Campylobacter jejuni. J Neurol. 1999 Dec;246(12):1204-6.
31 Huang EHZ, Lim SA, Lim PL et al. Retrobulbar optic neuritis after Hepatitis A vaccination in a HIV-infected patient Eye (Lond). 2009 Dec;23(12):2267-71
32 Kessler DA, the Working Group, Natanblut S, et al. A New Approach to Reporting Medication and Device Adverse Effects and Product Problems. JAMA. 1993; 269(21):2765-2768.
33 FDA.gov. Kessler DA. Introducing MEDWatch: A New Approach to Reporting Medication and Device Adverse Effects and Product Problems. Reprint from JAMA. June 9, 1993.
34 Braun M. Vaccine adverse event reporting system (VAERS): usefulness and limitations. Johns Hopkins Bloomberg School of Public Health
35 Rosenthanl S, Chen R. The reporting sensitivities of two passive surveillance systems for vaccine adverse events. Am J Public Health 1995; 85: pp. 1706-9.
36 AHRQ Electronic Support for Public Health–Vaccine Adverse Event Reporting System (ESP:VAERS) Dec 1, 2007-Sep. 30, 2010
37 U.S. Department of Health and Human Services. National Vaccine Injury Compensation Program Data—May 1, 2020. National Vaccine Injury Compensation Program. May. 1, 2020